Increased expression of LncRNA PANDAR predicts a poor prognosis in gastric cancer

Long non-coding RNAs (lncRNAs) are emerging as biomarkers and as important regulators in biological processes and tumorigenesis in cancer. PANDAR (promoter of CDKN1A antisense DNA damage activated RNA) serves as biomarkers and involves in development of multiple cancers. However, its clinical value of PANDAR in gastric cancer is still unknown. Hence, we carried out the present study aiming to identify the clinical significance of PANDAR in gastric cancer patients. We analyzed the expression levels of PANDAR in 100 paired gastric cancer tissues using Quantitative Real-time PCR. Our results showed that the expression of PANDAR was significantly increased in gastric cancer tissues compared with paired adjacent normal tissues. Furthermore, high expression of PANDAR was correlated with depth of invasion, TNM stage and lymphatic metastasis. Importantly, high expression of PANDAR could serve as an independent unfavorable prognostic role in gastric cancer. In conclusion, PANDAR may be a potential novel biomarker that predicts prognosis in gastric cancer.     

Up-regulated microRNA-155 expression is associated with poor prognosis in cervical cancer patients

BackgroundMicroRNAs (miRNAs) play important roles in tumor development and progression. The purposes of the study was to investigate the role of miR-155 in cervical cancer.MethodsQuantitative real-time RT-PCR (qRT-PCR) was performed to examine miR-155 expression in cervical cancer tissues and adjacent non-cancerous tissues. The association with overall survival of patients was analyzed by Kaplan-Meier survival analysis. Small interfering RNA (siRNA) was used to suppress miR-155 expression in cervical cancer cells. In vitro assays were performed to further explore the biological functions of miR-155 in cervical cancer.ResultsWe found that miR-155 expression was markedly up-regulated in cervical cancer tissues and correlated with FIGO stage, lymph nodes metastasis, vascular invasion and HPV. Patients with high miR-155 expression level had poorer overall survival than those with low miR-155 expression. Furthermore, multivariate Cox regression analysis suggested that increased miR-155 was an independent prognostic indicator for cervical cancer (P = 0.007; HR = 2.320; 95%CI: 1.259–4.276). Moreover, knockdown of miR-155 was demonstrated to inhibit cell proliferation, migration, and invasion in vitro.ConclusionOur study presents that miR-155 is a novel molecule involved in cervical cancer progression, which provide a potential prognostic biomarker and therapeutic target.     

胃癌卵巢转移的新近诊疗进展

胃癌是我国常见的恶性肿瘤,给我国造成了严重的疾病负担。胃癌可以发生卵巢转移,多见于43~48岁的绝经前女性。目前认为胃癌通过淋巴道转移的可能性更大,大多累及双侧卵巢,术中探查时发现的腹膜转移率很高,患者预后较差。诊断时需要结合胃癌病理及双侧卵巢肿瘤的影像学表现。目前治疗方法尚有争议,对术前评估可切除的单纯卵巢转移患者行根治性或者最大程度的减瘤手术,术后加以全身化疗及腹腔热灌注化疗可以提高总生存期。目前仍然需要更多大规模的研究数据进一步探讨有效的治疗方案。     

Up-regulation of miR-592 correlates with tumor progression and poor prognosis in patients with colorectal cancer

miR-592, as a potential biomarker, has been linked to several cancers. However, the expression level and prognostic value of miR-592 in CRC have not been elucidated. In this study, we detected the miR-592 expression in CRC serum, tumor tissues, adjacent non-tumor tissues (NATs) and four colorectal cancer cell lines by RT-PCR. Our data proved that miR-592 expression was up-regulated in clinical CRC serum and tissues (P < 0.05). Serum or tissue miR-592 in CRC metastatic patients also maintained a high level, compared to that in non-metastatic CRC patients (P < 0.05). After radical surgery, postoperative serum miR-592 level in CRC patients significantly decreased (P < 0.05). Our clinicopathological analysis revealed that high miR-592 was significant associated with the tumor size (P = 0.008), TNM stage (P = 0.026), distant metastasis (P = 0.004) and preoperative CEA level (P = 0.022), which led to a shorter overall survival rate in CRC patients (P = 0.032). Furthermore, we designed and transfected miR-592 mimics or inhibitors into the corresponding CRC lines, and our experiments in vitro demonstrated that miR-592 could promote cell proliferation, wound healing and invasion ability of CRC cells (P < 0.05), while miR-592 did not influence the CRC cell apoptosis (P > 0.05). All these results suggested that miR-592 functioned as a novel and potential carcinogen-initiated and metastasis-related biomarker in CRC, and down-regulation of miR-592 might be considered as a potentially significant molecular treatment strategy for CRC patients.     

Long noncoding RNA LUNAR1 associates with cell proliferation and predicts a poor prognosis in diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of B-cell lymphomas. Exploring a novel and important biomarker is indispensable for understanding the mechanism and clinical course of DLBCL. Emerging studies have shown that aberrant expression of long noncoding RNA (lncRNAs) is strongly associated with carcinogenesis. The aim of this study was to investigate the value of lncRNA LUNAR1 in DLBCL. Quantitative real-time PCR was performed to illustrate the patterns of LUNAR1 expression in tumor tissues and cell lines. The higher expression of LUNAR1 was significantly correlated with stage, rituximab and IPI. Univariate and multivariate analyses showed that LUNAR1 expression served as an independent predictor for overall survival and progression-free survival. Receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic values and the area under the ROC curve of LUNAR1 was up to 0.9420. Further experiments revealed that LUNAR1 knockdown significantly repressed cell proliferation of DLBCL by regulating E2F1, cyclin D1 and p21. In conclusion, our results indicate that LUNAR1 may serve as a candidate prognostic biomarker through growth regulation in DLBCL.     

PLK1和P53蛋白在卵巢上皮性癌中的表达及其意义

目的检测POLO样蛋白激酶1(PLK1)和P53蛋白在卵巢上皮性癌中的表达,探讨其与患者预后的关系。方法采用免疫组织化学SP法检测20例正常卵巢组织、19例卵巢良性上皮性肿瘤组织和52例卵巢上皮性癌组织中PLK1和P53蛋白的表达情况,分析其与卵巢癌临床病理指标的关系及二者在卵巢癌组织中表达的相关性,单因素和多因素Logistic回归分析影响卵巢癌患者预后的危险因素,Kaplan-Meier法分析PLK1和P53表达与卵巢癌患者预后的关系。结果 PLK1和P53在卵巢上皮性癌组织中的表达分别为38.5%和67.3%,显著高于良性肿瘤和正常卵巢组织(P<0.05)。在卵巢上皮性癌中,PLK1和P53异常高表达与临床分期和组织分化相关,临床分期越晚、组织分化越差的癌组织中PLK1和P53蛋白表达越高(P<0.05);PLK1蛋白的表达与P53蛋白的表达呈负相关(r=-0.629,P=0.000)。单因素Logistic回归分析显示PLK1、P53、临床分期、组织分化和淋巴结转移是影响卵巢癌患者预后的因素,多因素Logistic回归分析显示仅PLK1是影响卵巢癌患者预后的独立因素(OR=2.288,P=0.025,95%CI:0.105⁵0.050)。与其他患者相比,PLK1表达阳性同时P53表达阳性的卵巢癌患者,生存期最短(?2=17.246,P=0.037)。结论 PLK1和P53共同参与了卵巢癌的发生发展,PLK1可作为判断卵巢癌患者预后的标志物。     

血清肿瘤标记物与卵巢癌诊断和监控治疗的相关性研究

目的 探讨血清肿瘤标记物糖类抗原CA125、CA724、环氧化酶（COX-1）和人附睾蛋白4（HE4）联合动态检测在卵巢癌早期诊断和监控治疗、复发中的临床应用价值。方法选取82例卵巢癌患者（观察组）、79例卵巢良性病变患者（对照组）为研究对象,均经术后病理确诊。所有患者术前、术后均有血清肿瘤标记物CA125、CA724、COX—1、HE4检查资料,其中CA125、CA724、COX-1采用电化学发光法检测,HE4采用酶联免疫（ELISA）法检测,综舍评价四种肿瘤标记物联合动态检测在卵巢癌早期诊断和监控治疗、复发中的价值。结果卵巢癌组患者血清CA125、CA724、COX-1、HE4水平明显高于卵巢良性病变组（P〈0．01）;卵巢癌高分期（Ⅲ、Ⅳ期）组明显高于低分期（I、II）纽（P〈0．01）,卵巢癌术前、复发组与术后、无复发组血清肿瘤标记物水平差异有统计学意义（P（0．01）。CA125、CA724、COX-1、HE4诊断卵巢癌的敏感性分别为74．4％、70．7％、43．9％、69．5％,联合检测的敏感性高达96．3％,与各单项检测的敏感性比较差异有统计学意义（P〈0．01）。结论血清肿瘤标记物CA125、CA724、COX-1、HFA联合动态检测是卵巢癌早期诊断和监控治疗、复发的较好指标,有利于临床早期发现、早期干预。     

bFGF抗体抑制人卵巢癌裸鼠移植瘤细胞转移及血管新生的实验研究

目的 研究碱性成纤维细胞生长因子(b FGF)抗体对卵巢癌裸鼠移植瘤癌细胞转移和移植瘤组织血管新生的影响。方法 60只BALB/c裸鼠通过腹腔注射卵巢癌细胞建立人卵巢癌裸鼠移植瘤模型。1周后,60只卵巢癌移植瘤模型小鼠按照随机数字表法均分为3组,即模型组、溶剂组和b FGF抗体组。模型组不进行治疗,溶剂组腹腔注射b FGF抗体溶剂治疗,b FGF抗体组腹腔注射b FGF抗体治疗,共治疗7周。每组取10只小鼠让其自然死亡,记录并比较生存时间。实验第8周,每组安乐死10只小鼠。比较各组小鼠体重,卵巢癌移植瘤体积和重量,卵巢癌细胞转移结节数、转移器官数和转移病灶总数,以及卵巢癌移植瘤组织血管内皮生长因子(VEGF)表达水平、微血管数目以及凋亡细胞率。结果 b FGF抗体组小鼠各时间点体重和最终生存时间均显著高于模型组和溶剂组,差异均有统计学意义(P <0.05)。b FGF抗体组小鼠腹水体积、卵巢移植瘤体积和重量、癌细胞转移结节数、转移器官数和转移病灶总数均显著低于模型组和溶剂组,差异均有统计学意义(P <0.05); b FGF抗体组小鼠卵巢癌抑瘤率高于溶剂组,差异有统计学意义...     

KISS-1和基质金属蛋白酶-9在非小细胞肺癌中的表达及其与转移和预后的关系

目的：检测KISS-1蛋白和MMP-9蛋白在一组非小细胞肺(non-small cell lung cancer,NSCLC)中的表达，旨在探讨其表达水平与转移和预后的关系。方法：采用免疫组化(Elivision) 法检测85例非小细胞肺癌和56例对应转移的淋巴结标本中KISS-1和MMP-9蛋白的表达水平，用图像分析方法测定其积分光密度(integral optical density，IOD)。结果：(1)KISS-1在I ~II期NSCLC 、无转移NSCLC组、原发灶中的表达分别高于III~IV 期NSCLC 、有转移NSCLC组、淋巴结转移灶中的表达水平(p<0.05)；(2)MMP-9在腺癌、肿瘤直径≤3cm NSCLC组、I ~II期NSCLC 、无转移NSCLC组、原发灶中的表达分别低于鳞癌、肿瘤直径>3cm组NSCLC、 III~IV 期NSCLC、有转移组NSCLC、淋巴结转移灶中的表达水平 (p<0.05)；(3)在NSCLC中，KISS-1和 MMP-9的表达水平呈负相关(r=-0.523, p <0.01)；(4)KISS-1蛋白高表达组患者的术后五年生存率(20.9%)显著高于低表达组 (2.4%) (p<0.01)，而MMP-9高表达组患者的术后五年生存率(4.7%)显著低于低表达组(19%) (p<0.05)。结论：KISS-1的弱表达和MMP-9的强表达可能与NSCLC的转移有关，二者的失衡可能是造成转移的一个原因。     

卵巢癌患者血清中12种肿瘤标志物的含量检测

目的　探讨多肿瘤标志物蛋白芯片诊断系统 (C 12 )定量测定 12种肿瘤标志物在卵巢癌患者血清中的表达情况 ,并筛选出阳性率较高的若干标志物 ,为临床诊断提供依据。方法　用C 12定量测定 36例卵巢癌患者、32例良性卵巢疾病患者和 39名正常人血清的 12种肿瘤标志物 ,包括糖链抗原 12 5 (CA12 5 )、铁蛋白、癌胚抗原 (CEA)、甲胎蛋白 (AFP)、糖链抗原 199(CA199)、糖链抗原 15 3(CA15 3)、神经原特异性烯醇化酶 (NSE)、糖链抗原 2 4 2 (CA2 4 2 )、前列腺特异性抗原 (PSA)、游离前列腺特异性抗原 (f PSA)、生物激素 (HGH)和人绒毛膜促性腺激素 (β HCG)。 结果　卵巢癌组CA12 5、铁蛋白、CEA的检测结果较其他 2组差异有极其显著性 (P <0 .0 1) ,CA199、CA2 4 2的检测结果较其他 2组差异有显著性 (P <0 .0 5 )。联合检测的灵敏度 88.9% ,特异性87.3% ,阳性预测值为 78% ,阴性预测值为 93.9% ,准确度为 87.9% ,灵敏度从CA12 5单指标的 6 9.4 %提高到88.9%。结论　肿瘤标志物CA12 5、CA199、CA2 4 2多指标联合检测提高了恶性卵巢癌诊断阳性率 ,为处于亚临床期的卵巢癌患者及正常体检人群中卵巢肿瘤的早期检出提供了可靠的检测方法。     

Sema3C promotes hepatic metastasis and predicts poor prognosis in gastric adenocarcinoma

ObjectiveSemaphorin 3C (Sema3C) may regulate tumor metastasis and prognosis. We determined the biological roles of Sema3C in the hepatic metastasis of gastric adenocarcinoma and evaluated its clinical significance as a potential biomarker.MethodsSema3C expression in gastric cancer (GC) cell lines and tissues was measured using RT-qPCR and western blotting. Moreover, Sema3C functions were analyzed using Transwell assays and in vitro metastasis assays in gain- and loss-of-function experiments. Furthermore, the impact of Sema3C on the prognosis of 80 randomly selected patients with GC was investigated by immunohistochemistry. Additionally, the expression of epithelial-mesenchymal transition (EMT) indicators was verified by immunohistochemistry in GC tissues.ResultsSema3C expression was significantly upregulated in highly metastatic GC cell lines and tissues. Additionally, Sema3C promoted invasion, migration and hepatic metastasis in GC cells. Moreover, Sema3C expression was positively correlated with clinicopathological features in GC and paired hepatic metastatic tissues, and Sema3C expression was an independent prognostic factor. Finally, Sema3C expression was associated with node metastasis, hepatic metastasis and EMT marker expression.ConclusionsSema3C may play roles in regulating the EMT and metastasis of gastric adenocarcinoma, highlighting its potential use as a prognostic factor for hepatic metastasis and poor prognosis in gastric adenocarcinoma.     

Identification of a four-miRNA signature predicts the prognosis of papillary thyroid cancer

BACKGROUNDIn recently diagnosed patients with thyroid cancer, papillary thyroid cancer (PTC), as the most common histological subtype, accounts for 90% of all cases. Although PTC is known as a relatively adolescent malignant disease, there still is a high possibility of recurrence in PTC patients with a poor prognosis. Therefore, new biomarkers are necessary to guide more effective stratification of PTC patients and personalize therapy to avoid overtreatment or inadequate treatment. Accumulating evidence demonstrates that microRNAs (miRNAs) have broad application prospects as diagnostic biomarkers in cancer.AIMTo explore novel markers consisting of miRNA-associated signatures for PTC prognostication.METHODSWe obtained and analyzed the data of 497 PTC patients from The Cancer Genome Atlas. The patients were randomly assigned to either a training or testing cohort.RESULTSWe discovered 237 differentially expressed miRNAs in tumorous thyroid tissues compared with normal tissues, which contained 172 up-regulated and 65 down-regulated miRNAs. The evaluation of differently expressed miRNAs was conducted using our risk score model. We then successfully generated a four-miRNA potential prognostic signature [risk score = (-0.001 × hsa-miR-181a-2-3p) + (0.003 × hsa-miR-138-5p) + (-0.018 × hsa-miR-424-3p) + (0.284 × hsa-miR-612)], which reliably distinguished patients from high and low risk with a significant difference in the overall survival (P < 0.01) and was effective in predicting the five-year disease survival rate with the area under the receiver operating characteristic curve of 0.937 and 0.812 in the training and testing cohorts, respectively. Additionally, there was a trend indicated that high-risk patients had shorter relapse-free survival, although statistical significance was not reached (P = 0.082) in our sequencing cohort.CONCLUSIONOur results indicated a four-miRNA signature that has a robust predictive effect on the prognosis of PTC. Accordingly, we would recommend more radical therapy and closer follow-ups for high-risk groups.     

卵巢癌合并卵巢脓肿一例

卵巢癌是常见的妇科恶性肿瘤,其早期病变因症状及体征不明显且起病隐匿,故缺乏有效的筛查手段。卵巢癌合并卵巢脓肿或者卵巢脓肿恶变为卵巢癌在临床上发病率极低,确诊需要依赖临床实验室、病理及免疫组织化学等相关检查,治疗以手术为主,辅以化学治疗联合或不联合靶向治疗,临床疗效欠佳。该文结合病历资料及相关文献进行回顾性分析,对1例卵巢腺癌合并卵巢脓肿的临床特点及其诊治方法进行总结报道,以期引起临床医师的重视,提高对这类疾病的认识,为该类疾病的诊断和治疗提供支持。     

DMU-212 inhibits tumor growth in xenograft model of human ovarian cancer

DMU-212 has been shown to evoke a mitochondrial apoptotic pathway in transformed fibroblasts and breast cancer. However, recently published data indicated the ability of DMU-212 to evoke apoptosis in both mitochondria- and receptor-mediated manner in two ovarian cancer cell lines, namely A-2780 and SKOV-3, which showed varied sensitivity to the compound tested. The pronounced cytotoxic effects of DMU-212 observed in A-2780 cells were related to the execution of extracellular apoptosis pathway and cell cycle arrest in G2/M phase. In view of the great anticancer potential of DMU-212 against A-2780 cell line, the aim of the current study was to assess antiproliferative activity of DMU-212 in xenograft model of ovarian cancer. To evaluate in vitro metabolic properties of cells that were to be injected into SCID mice, uptake and decline of DMU-212 in A-2780 ovarian cancer cell line was investigated. It was found that the concentration of the test compound in A-2780 cells was growing within first eight hours, and then the gradual decline was observed. A-2780 cells stably transfected with pcDNA3.1/Zeo(-)-Luc vector were subcutaneously inoculated into the right flanks of SCID mice. After seven days of the treatment with DMU-212 (50 mg/kg b.w), tumor growth appeared to be suppressed in the animals treated with the compound tested. At day 14 of the experiment, tumor burden in mice treated with DMU-212 was significantly lower, as compared to untreated controls. Our findings suggest that DMU-212 might be considered as a potential anticancer agent used in ovarian cancer therapy.